This proposal outlines a series of Phase I trials testing the use of intensive doses of standard multiagent chemotherapy, multiagent chemotherapy with newer drugs, and a radiolabeled monoclonal antibody, all with autologous hematopoietic cell support (AHCS), to improve the treatment of patients with advanced or high risk breast cancer. Each trial will be accompanied by a total pharmacokinetic (PK) and pharmacodynamic analysis of each component of the treatment and various clinical outcomes. The goal os to produce an intensive multicomponent treatment regimen capable of substantial improvement in the treatment of previously incurable breast cancer. Based on eight years of prior experience with the cyclophosphamide/cisplatin/BCNU (CPA/cDDP/BCNU) combination with AHCS, we will perform Phase I trials of the combination of Taxol/CPA/cDDP, Taxol/CPA/cDDP/BCNU, and a randomized trial of CPA/cDDP/BCNU where the research arm will test administration of BCNU using a PK-directed model. These trials emphasize single drug or strategy modifications of previous regimens to allow easiest interpretation of outcome. An intensively dosed radiolabeled anti-breast cancer monoclonal antibody will also be studied. Phase II trials of the optimal of these approaches and combinations of them are proposed. Finally, a multicomponent multimodality regimen will be developed to incorporate a maximal effort to improve treatment activity in this area.